CN115108874A - Amine azide chiral compound, bis-azide chiral compound and related preparation methods - Google Patents
Amine azide chiral compound, bis-azide chiral compound and related preparation methods Download PDFInfo
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- CN115108874A CN115108874A CN202110291938.3A CN202110291938A CN115108874A CN 115108874 A CN115108874 A CN 115108874A CN 202110291938 A CN202110291938 A CN 202110291938A CN 115108874 A CN115108874 A CN 115108874A
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- azide
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- -1 Amine azide Chemical class 0.000 title claims abstract description 77
- 150000001875 compounds Chemical class 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 134
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 claims abstract description 72
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 70
- 239000003446 ligand Substances 0.000 claims abstract description 55
- 239000000126 substance Substances 0.000 claims abstract description 29
- 229910052742 iron Inorganic materials 0.000 claims abstract description 27
- RCZCNTFZEKSGNH-UHFFFAOYSA-N C1=CC=CC=2OC3=C(C21)C=CC=C3.O3C=NCC3 Chemical compound C1=CC=CC=2OC3=C(C21)C=CC=C3.O3C=NCC3 RCZCNTFZEKSGNH-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 195
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 36
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 27
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
- 125000003107 substituted aryl group Chemical group 0.000 claims description 23
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 claims description 21
- 239000003960 organic solvent Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 15
- SHZIWNPUGXLXDT-UHFFFAOYSA-N caproic acid ethyl ester Natural products CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- YKTNISGZEGZHIS-UHFFFAOYSA-N 2-$l^{1}-oxidanyloxy-2-methylpropane Chemical group CC(C)(C)O[O] YKTNISGZEGZHIS-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 150000005840 aryl radicals Chemical class 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 238000005086 pumping Methods 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 7
- 239000005416 organic matter Substances 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- FHIVAFMUCKRCQO-UHFFFAOYSA-N diazinon Chemical compound CCOP(=S)(OCC)OC1=CC(C)=NC(C(C)C)=N1 FHIVAFMUCKRCQO-UHFFFAOYSA-N 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- MCDLETWIOVSGJT-UHFFFAOYSA-N acetic acid;iron Chemical compound [Fe].CC(O)=O.CC(O)=O MCDLETWIOVSGJT-UHFFFAOYSA-N 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 229960002089 ferrous chloride Drugs 0.000 claims description 2
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- PVFSDGKDKFSOTB-UHFFFAOYSA-K iron(3+);triacetate Chemical compound [Fe+3].CC([O-])=O.CC([O-])=O.CC([O-])=O PVFSDGKDKFSOTB-UHFFFAOYSA-K 0.000 claims description 2
- OSHOQERNFGVVRH-UHFFFAOYSA-K iron(3+);trifluoromethanesulfonate Chemical compound [Fe+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F OSHOQERNFGVVRH-UHFFFAOYSA-K 0.000 claims description 2
- FZGIHSNZYGFUGM-UHFFFAOYSA-L iron(ii) fluoride Chemical compound [F-].[F-].[Fe+2] FZGIHSNZYGFUGM-UHFFFAOYSA-L 0.000 claims description 2
- SHXXPRJOPFJRHA-UHFFFAOYSA-K iron(iii) fluoride Chemical compound F[Fe](F)F SHXXPRJOPFJRHA-UHFFFAOYSA-K 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 150000002894 organic compounds Chemical class 0.000 claims 1
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 abstract description 26
- 150000003254 radicals Chemical class 0.000 abstract description 7
- 239000000376 reactant Substances 0.000 abstract description 6
- 230000003197 catalytic effect Effects 0.000 abstract description 5
- 238000006396 nitration reaction Methods 0.000 abstract description 5
- 150000001540 azides Chemical class 0.000 abstract description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 abstract 1
- ICCBZGUDUOMNOF-UHFFFAOYSA-N azidoamine Chemical compound NN=[N+]=[N-] ICCBZGUDUOMNOF-UHFFFAOYSA-N 0.000 abstract 1
- 238000006193 diazotization reaction Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 115
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- 238000005481 NMR spectroscopy Methods 0.000 description 68
- 239000000047 product Substances 0.000 description 61
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 59
- 239000011261 inert gas Substances 0.000 description 58
- 239000002904 solvent Substances 0.000 description 58
- 238000001514 detection method Methods 0.000 description 47
- 239000011734 sodium Substances 0.000 description 38
- 238000004440 column chromatography Methods 0.000 description 31
- 239000012043 crude product Substances 0.000 description 31
- 238000004128 high performance liquid chromatography Methods 0.000 description 30
- 230000014759 maintenance of location Effects 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 238000001914 filtration Methods 0.000 description 26
- 238000007865 diluting Methods 0.000 description 25
- 239000002994 raw material Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000000375 direct analysis in real time Methods 0.000 description 11
- 238000012063 dual-affinity re-targeting Methods 0.000 description 11
- 238000004821 distillation Methods 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 150000001336 alkenes Chemical class 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- BOVQCIDBZXNFEJ-UHFFFAOYSA-N 1-chloro-3-ethenylbenzene Chemical compound ClC1=CC=CC(C=C)=C1 BOVQCIDBZXNFEJ-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- BJQFWAQRPATHTR-UHFFFAOYSA-N 1,2-dichloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1Cl BJQFWAQRPATHTR-UHFFFAOYSA-N 0.000 description 3
- ZRZHXNCATOYMJH-UHFFFAOYSA-N 1-(chloromethyl)-4-ethenylbenzene Chemical compound ClCC1=CC=C(C=C)C=C1 ZRZHXNCATOYMJH-UHFFFAOYSA-N 0.000 description 3
- IUCFIBLGZMOMQM-UHFFFAOYSA-N 1-bromo-4-ethenyl-2-methylbenzene Chemical compound CC1=CC(C=C)=CC=C1Br IUCFIBLGZMOMQM-UHFFFAOYSA-N 0.000 description 3
- XKMDZVINHIFHLY-UHFFFAOYSA-N 1-ethenyl-3,5-dimethylbenzene Chemical compound CC1=CC(C)=CC(C=C)=C1 XKMDZVINHIFHLY-UHFFFAOYSA-N 0.000 description 3
- ZJSKEGAHBAHFON-UHFFFAOYSA-N 1-ethenyl-3-fluorobenzene Chemical compound FC1=CC=CC(C=C)=C1 ZJSKEGAHBAHFON-UHFFFAOYSA-N 0.000 description 3
- PECUPOXPPBBFLU-UHFFFAOYSA-N 1-ethenyl-3-methoxybenzene Chemical compound COC1=CC=CC(C=C)=C1 PECUPOXPPBBFLU-UHFFFAOYSA-N 0.000 description 3
- JZHGRUMIRATHIU-UHFFFAOYSA-N 1-ethenyl-3-methylbenzene Chemical compound CC1=CC=CC(C=C)=C1 JZHGRUMIRATHIU-UHFFFAOYSA-N 0.000 description 3
- CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 3
- LCESPRDNNUVABS-UHFFFAOYSA-N 2-bromo-4-ethenyl-1-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1Br LCESPRDNNUVABS-UHFFFAOYSA-N 0.000 description 3
- YKEAXNQRVSFQSI-UHFFFAOYSA-N 2-chloro-4-ethenyl-1-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1Cl YKEAXNQRVSFQSI-UHFFFAOYSA-N 0.000 description 3
- UEPFNQXGOLWTAD-UHFFFAOYSA-N 2-ethenyl-1-benzothiophene Chemical compound C1=CC=C2SC(C=C)=CC2=C1 UEPFNQXGOLWTAD-UHFFFAOYSA-N 0.000 description 3
- JMOIDWXRUSAWHV-UHFFFAOYSA-N 4-ethenyl-1-fluoro-2-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C=C)C=C1C(F)(F)F JMOIDWXRUSAWHV-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VPKZWIGZODEBDP-UHFFFAOYSA-N 4-ethenyl-1,2-difluorobenzene Chemical compound FC1=CC=C(C=C)C=C1F VPKZWIGZODEBDP-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 150000001924 cycloalkanes Chemical class 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- WJUBHMWKRGTJPD-UHFFFAOYSA-N 2-[3-(4-chlorophenyl)-4-oxoquinazolin-2-yl]sulfanyl-n-(4-sulfamoylphenyl)acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC(=O)CSC1=NC2=CC=CC=C2C(=O)N1C1=CC=C(Cl)C=C1 WJUBHMWKRGTJPD-UHFFFAOYSA-N 0.000 description 1
- AECYNISFOBUPBN-BJKOFHAPSA-N CC(C)(C)C(C)(C)C1=CC=C([C@@H]([C@@H](C2=CC=C(C(C)(C)C(C)(C)C)C=C2)O)N)C=C1 Chemical compound CC(C)(C)C(C)(C)C1=CC=C([C@@H]([C@@H](C2=CC=C(C(C)(C)C(C)(C)C)C=C2)O)N)C=C1 AECYNISFOBUPBN-BJKOFHAPSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- ANUMPVYFVKVWHW-VQTJNVASSA-N N[C@H]([C@H](O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C(C)(C)C Chemical compound N[C@H]([C@H](O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C(C)(C)C ANUMPVYFVKVWHW-VQTJNVASSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ZVQXQPNJHRNGID-UHFFFAOYSA-N tetramethylsuccinonitrile Chemical compound N#CC(C)(C)C(C)(C)C#N ZVQXQPNJHRNGID-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
- C07C247/08—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated
- C07C247/10—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses an amine azide chiral compound, a bis-azide chiral compound and a preparation method thereof. The amine azide chiral compound is selected from any one of substances with a structural formula shown in a formula I, and the double azide chiral compound is selected from any one of substances with structural formulas shown in a formula i (a) or i (b). The method utilizes iron to catalyze asymmetric amine azide reaction. The reaction is that dibenzofuran oxazoline ligand is used as a chiral catalytic center, iron is used for catalyzing asymmetric azido amine nitration reaction through a free radical mechanism, and NFSI and azidotrimethylsilane are used as efficient and controllable reactants to be introduced into the asymmetric amine-nitration reaction for the first time. The application utilizes iron to catalyze asymmetric double-azide reactions. The reaction is characterized in that dibenzofuran oxazoline ligands are used as chiral catalytic centers, the iron-catalyzed asymmetric azido diazotization reaction is realized through a free radical mechanism, and azidotrimethylsilane is introduced into the asymmetric dinitrotization reaction as an efficient and controllable reactant for the first time.
Description
Technical Field
The application relates to an amine azide chiral compound, a bis-azide chiral compound and related preparation methods, and belongs to the technical field of organic synthesis.
Background
The amine-azide reaction of olefins has been widely and intensively studied since the twenty-first century. However, no studies have been reported on the preparation of amine azides from olefins corresponding to selective products. The reason why asymmetric amine-azide reaction of olefin has not been reported is that a radical mechanism is experienced during the reaction, and the radical mechanism is widely considered to be not easy to control stereoselectivity. For these reasons, no studies have been reported for asymmetric amine-azide reactions of olefins.
Disclosure of Invention
According to one aspect of the present application, there is provided an amine azide chiral compound, which describes an iron-catalyzed asymmetric amine azide reaction. The reaction is that dibenzofuran oxazoline ligand is used as a chiral catalytic center, and the iron-catalyzed asymmetric diamine nitration reaction is realized through a free radical mechanism. The method introduces NFSI and azidotrimethylsilane as efficient and controllable reactants into an asymmetric amine-nitridation reaction for the first time, has the advantages of cheap raw materials and catalysts, mild reaction conditions, simple operation, high reaction efficiency, high corresponding selectivity and the like, and can be prepared in a large scale.
An amine azide chiral compound selected from any one of the substances having the structural formula shown in formula I:
in formula I, R 1 Is selected from C 6 ～C 10 Aryl radicals I, C 6 ～C 10 Substituted aryl radicals I, C 8 ～C 12 Any one of heteroaryl I.
Optionally, the C 6 ～C 10 The substituted aryl I is selected from any one of groups with a structural formula shown in a formula II;
in formula II, R 2 Selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 3 selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 4 selected from H, C 1 ～C 4 Any of alkyl groups;
and R is 2 、R 3 、R 4 At most two of which are H.
Alternatively, in formula ii, R4 is hydrogen.
Specifically, the C 6 ～C 10 The substituted aryl I is selected from any one of groups with a structural formula shown in a formula II-1;
in the formula II-1, R 21 Selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 31 selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
and, R 21 And R 31 At most one of them is H.
Alternatively, in formula II, R 3 Is hydrogen, R 2 Is selected from C 1 ～C 4 Any one of alkyl, R 4 Is selected from C 1 ～C 4 Any of alkyl groups.
Specifically, the C 6 ～C 10 The substituted aryl I is selected from any one of groups with a structural formula shown in a formula II-2;
in the formula II-2, R 22 Is selected from C 1 ～C 4 Alkyl radical, R 42 Is selected from C 1 ～C 4 An alkyl group.
Optionally, the C 8 ～C 12 The heteroatom in heteroaryl I includes S.
Alternatively, the R is 1 Any one selected from the group having the following structural formula;
according to a second aspect of the present application, there is also provided a process for the preparation of the amine azide chiral compound of any one of the above, the process comprising: reacting a mixture containing N-fluoro-diphenyl sulfonyl imine, a compound II containing a carbon-carbon double bond and azido trimethylsilane in the presence of a catalyst to obtain the amine azide chiral compound;
the catalyst comprises an iron source and a dibenzofuran oxazoline ligand;
the compound II containing the carbon-carbon double bond is selected from any one of substances with a structural formula shown in a formula III;
r in formula III 1 And R in formula I 1 The same is true.
In particular, in the formulaIn III, R 1 Is selected from C 6 ～C 10 Aryl radicals I, C 6 ～C 10 Substituted aryl radicals I, C 8 ～C 12 Any one of heteroaryl I.
Optionally, the compound II containing the carbon-carbon double bond is selected from any one of substances with a structural formula shown in a formula III-1;
in the formula III-1, R 2 Selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 3 selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 4 selected from H, C 1 ～C 4 Any of alkyl groups;
and, R 2 、R 3 、R 4 At most two of which are H.
Optionally, the compound II containing the carbon-carbon double bond is selected from any one of substances with structural formulas shown in formulas III-11;
in the formula III-11, R 21 Selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 31 selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
and, R 21 And R 31 At most one of which is H.
Optionally, the compound II containing the carbon-carbon double bond is selected from any one of substances with structural formulas shown in formulas III-12;
in the formula III-12, R 22 Is selected from C 1 ～C 4 Alkyl radical, R 42 Is selected from C 1 ～C 4 An alkyl group.
Optionally, the C 8 ～C 12 The heteroatom in heteroaryl I includes S.
Optionally, the compound II containing the carbon-carbon double bond is selected from any one of the substances with the following structural formula;
optionally, the iron source comprises Fe 3+ Source or Fe 2+ A source;
said Fe 3+ The source comprises any one of ferric acetate, ferric chloride and ferric fluoride;
said Fe 2+ The source comprises any one of ferrous trifluoromethanesulfonate, ferrous acetate, ferrous chloride and ferrous fluoride.
Optionally, the dibenzofuran oxazoline ligand is selected from any one of substances with a structural formula shown in a formula V;
in formula V, R 5 And R 8 Each of which isIndependently selected from hydrogen, C 1 ～C 12 Alkyl radical, C 6 ～C 24 Aryl radical, C 6 ～C 24 Heteroaryl group, C 6 ～C 24 One of substituted aryl; r is 6 And R 7 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 6 ～C 24 Aryl radical, C 6 ～C 24 Heteroaryl group, C 6 ～C 24 One of substituted aryl groups.
Optionally, the dibenzofuran oxazoline ligand is selected from any one of substances with a structural formula shown in formula V-1;
in the formula V-1, R 51 、R 61 、R 71 、R 81 Are the same group;
R 51 、R 61 、R 71 、R 81 is selected from C 8 ～C 16 Any of substituted aryl groups.
Optionally, the C 8 ～C 16 The substituted aryl is selected from any one of groups with a structural formula shown in a formula VI;
in formula VI, R 9 Is selected from C 4 ～C 7 Any of alkyl groups.
Optionally, the molar ratio of the iron source to the dibenzofuran oxazoline ligand is 1:1 to 1.5.
Preferably, in the reaction system, the molar ratio of the iron source to the ligand is 1: 1.2-1: 1.5.
optionally, the molar ratio of the N-fluoro bis benzenesulfonylimine to the azidotrimethylsilane to the compound II containing the carbon-carbon double bond is 1-10: 1-10: 1.
Preferably, the molar ratio of the N-fluoro-bis-benzenesulfonylimide to the azidotrimethylsilane to the compound II containing a carbon-carbon double bond is 1.25 to 2.5:1.
The molar ratio of NFSI to compound II with a carbon-carbon double bond in the reaction system is 1: 1-10: 1.
Further preferably, in the reaction system, the molar ratio of NFSI to the compound III having a carbon-carbon double bond in the reaction system is 1:1 to 3: 1.
The molar ratio of azidotrimethylsilane to the compound II having a carbon-carbon double bond in the reaction system is 1: 1-10: 1.
In the reaction system, the molar ratio of azidotrimethylsilane to the compound III having a carbon-carbon double bond in the reaction system is more preferably 1:1 to 3: 1.
Optionally, the molar ratio of the iron source to the compound II containing the carbon-carbon double bond is 0.5-10: 100.
Specifically, the upper limit of the molar ratio of the iron source to the compound II containing a carbon-carbon double bond is selected from 1:100, 5:100, 7:100, 10: 100; the lower limit of the molar ratio of the iron source to the compound II containing a carbon-carbon double bond is selected from 0.5:100, 1:100, 3:100, 5:100, 7: 100.
Optionally, the reaction conditions are: the reaction temperature is not more than 50 ℃, and the reaction time is not less than 6 minutes.
Optionally, the reaction conditions are: the reaction temperature is 20-50 ℃, and the reaction time is 48-72 h.
Optionally, the mixture further comprises an organic solvent;
the organic solvent comprises at least one of chloroform, dichloromethane, carbon tetrachloride and diethyl ether.
Optionally, the ratio of the volume of the organic solvent to the number of moles of the compound II containing a carbon-carbon double bond is 1.0 to 2.0 mL/mmol.
Possible preparation methods are described below:
s100, mixing an iron source, a dibenzofuran oxazoline ligand and an organic solvent, stirring under an inert condition, and pumping away the organic solvent a to obtain a material a;
s200, adding an organic solvent b, N-fluoro-bis-benzenesulfonylimine, a compound II containing carbon-carbon double bonds and azidotrimethylsilane into the material a under an inert condition, and reacting to obtain the amine azide chiral compound.
According to a third aspect of the application, there is also provided a chiral organic diazide compound selected from any one of the substances having a structural formula shown in formula i (a) or formula i (b);
in formula i (a), R 'and R' are independently selected from H, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Substituted alkyl, C 6 ～C 10 Aryl radical, C 6 ～C 10 Any of substituted aryl groups;
said C is 1 ～C 4 The substituent in the substituted alkyl is adamantyl;
R 1 the same as in formula I;
in formula i (b), n is 0 or 1; r 1 The same as in formula I.
According to a fourth aspect of the present application, there is also provided a preparation method of the chiral organic matter with diazide, the preparation method including:
reacting a mixture containing tert-butyl peroxy (2-ethylhexanoate), azidotrimethylsilane and a substance a containing carbon-carbon double bonds in the presence of a catalyst to obtain the chiral organic matter of bis-azido;
the catalyst comprises an iron source and a dibenzofuran oxazoline ligand;
the substance a containing the carbon-carbon double bond is selected from any one of substances shown in formula i-1 or formula i-2;
wherein R is 1 The same as in formula I; r ', R' are the same as in formula i (a); n is the same as formula i (b).
Optionally, the substance a containing carbon-carbon double bonds is selected from any one of the following substances;
optionally, the iron source comprises Fe 3+ Source or Fe 2+ A source; said Fe 3+ The source comprises ferric triflate; said Fe 2+ The source comprises ferrous triflate.
Optionally, the dibenzofuran oxazoline ligand is selected from any one of substances with a structural formula shown in a formula V;
in formula V, R 5 And R 8 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 6 ～C 24 Aryl radical, C 6 ～C 24 Heteroaryl group, C 6 ～C 24 One of substituted aryl; r 6 And R 7 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 6 ～C 24 Aryl radical, C 6 ～C 24 Heteroaryl, C 6 ～C 24 One of substituted aryl groups.
Optionally, the dibenzofuran oxazoline ligand is selected from any one of substances with a structural formula shown in formula V-1;
in the formula V-1, R 51 、R 61 、R 71 、R 81 Are the same group; r 51 、R 61 、R 71 、R 81 Is selected from C 8 ～C 16 Any of substituted aryl groups.
Optionally, the C 8 ～C 16 The substituted aryl is selected from any one of groups with a structural formula shown in a formula VI;
in formula VI, R 9 Is selected from C 4 ～C 7 Any of alkyl groups.
Optionally, the molar ratio of the iron source to the dibenzofuran oxazoline ligand is 1:1 to 1.5.
Optionally, the molar ratio of the tert-butyl peroxy (2-ethylhexanoate), the azidotrimethylsilane to the compound a containing a carbon-carbon double bond is 0.5-1.0: 0.1-0.3.
Optionally, the molar ratio of the iron source to the compound a containing the carbon-carbon double bond is 1-10: 100.
Optionally, the reaction conditions are: the reaction temperature is not more than 50 ℃, and the reaction time is not less than 6 minutes.
Optionally, the reaction conditions are: the reaction temperature is 20-50 ℃, and the reaction time is 48-72 h.
Optionally, the mixture further comprises an organic solvent; the organic solvent comprises at least one of chloroform, dichloromethane, carbon tetrachloride and diethyl ether.
Optionally, the ratio of the volume of the organic solvent to the number of moles of the compound a containing a carbon-carbon double bond is 1.0 to 2.0 mL/mmol.
Optionally, the preparation method comprises:
s100, mixing an iron source and a dibenzofuran oxazoline ligand with an organic solvent a, stirring under an inert condition, and pumping away the organic solvent a to obtain a material a;
s200, adding an organic solvent b, tert-butyl peroxy (2-ethylhexanoate), a compound a containing carbon-carbon double bonds and azidotrimethylsilane into the material a under an inert condition, and reacting to obtain the chiral organic matter of diazide.
Optionally, the reaction conditions are: the reaction temperature is 20-50 ℃, and the reaction time is 48-72 h.
Optionally, the ratio of the volume of the organic solvent to the number of moles of the compound a containing a carbon-carbon double bond is 1.0 to 2.0 mL/mmol.
The method utilizes iron to catalyze asymmetric amine azide reaction. The reaction is that dibenzofuran oxazoline ligand is used as a chiral catalytic center, and iron is used for catalyzing asymmetric azide nitration reaction through a free radical mechanism. The method introduces NFSI and azidotrimethylsilane into asymmetric amine-nitridation reaction as efficient and controllable reactants for the first time, has the advantages of cheap raw materials and catalysts, mild reaction conditions, simple operation, high reaction efficiency, high corresponding selectivity and the like, and can be prepared in a large scale. The application utilizes iron to catalyze asymmetric double-azide reactions. The reaction is that dibenzofuran oxazoline ligand is used as a chiral catalytic center, and the iron-catalyzed asymmetric diamine nitration reaction is realized through a free radical mechanism. The method introduces azidotrimethylsilane into asymmetric double-nitridation reaction as an efficient and controllable reactant for the first time, and has the advantages of cheap raw materials and catalysts, mild reaction conditions, simple operation, high reaction efficiency, high corresponding selectivity and the like.
In this application, C 6 ～C 10 、C 8 ～C 12 The number of carbon atoms included in the group;
in this application, the term "aryl" refers to a group formed by the loss of one hydrogen atom on an aromatic ring on an aromatic compound molecule.
In the present application, the term "substituted aromatic hydrocarbon group" refers to a group formed by substituting at least one hydrogen atom on an aryl group with a substituent.
In the present application, the term "heteroaryl" refers to a group formed by the loss of any one hydrogen atom from an aromatic ring in an aromatic compound molecule having a heterocyclic aromatic ring.
The term "alkyl" is a group formed by the loss of any one hydrogen atom from the molecule of an alkane compound including straight-chain alkanes, branched alkanes, cycloalkanes, and branched cycloalkanes.
In this application, -t-Bu is tert-butyl.
-Ph is phenyl;
-MeO is methoxy;
NFSI is N-fluoro bis benzenesulfonylimine;
TMSN 3 is azidotrimethylsilane.
The beneficial effects that this application can produce include:
(1) according to the asymmetric alkene amine-azide reaction method, NFSI and trimethylsilyl azide are used as efficient and controllable reactants and are introduced into an asymmetric amine-nitridation reaction for the first time.
(2) The asymmetric alkene amine-azide reaction method provided by the application has the advantages of cheap raw materials and catalysts, mild reaction conditions, simplicity in operation, high reaction efficiency and the like.
(3) Compared with the prior art, the asymmetric amine-azide reaction method for olefin realizes asymmetric azide reaction for the first time.
Detailed Description
The present application will be described in detail with reference to examples, but the present application is not limited to these examples.
Unless otherwise specified, the raw materials and catalysts in the examples of the present application were all purchased commercially.
In the examples, NMR spectra 1 H-NMR was measured on a 400AVANCE model III Spectrometer (Spectrometer) from Bruker, 400MHz, CDCl 3 (ii) a Carbon spectrum 13 C-NMR，400MHz，CDCl 3 。
The product separation adopts an RF + UV-VIS type full-automatic rapid preparation chromatographic system of Teledyne Isco.
The high-molecular mass spectrometer was measured on an Impact II UHR-TOF from Bruker, Inc. (Bruker), purchased from the institute of Fujian materials, China, Japan, by HRMS (ESI).
The yield of the compound having a non-terminal double bond was calculated by the following formula:
yield%
The dibenzofuran oxazoline ligands used in the examples of the present application were prepared as follows:
the preparation method of the ligand L1 comprises the following steps:
1) 84mg (0.5mmol) of dibenzofuran and 2mL (2.5mmol) of n-butyllithium (n-BuLi) were charged into a reaction tube, reacted at-78 ℃ for 1 hour, and then allowed to react at room temperature for 24 hours. After 24 hours, the mixture was placed at-78 ℃ and carbon dioxide (CO) was introduced 2 ) For 1 hour. Acidifying with hydrochloric acid (HCl) and pumping to obtain diacid product.
2) The diacid is loaded into a reaction tube, and thionyl chloride (SOCl) is added 2 ) mu.L (1.25mmol) was reacted at 70 ℃ for 3 hours to give the acid chloride product.
3) The acid chloride was slowly added dropwise to a reaction tube containing 613mg (1.5mmol) of amino alcohol ((1R,2S) -2-amino-1,2-bis (4- (2,3,3-trimethylbutan-2-yl) phenyl) ethane-1-ol) and 207. mu.L (1.5mmol) of Triethylamine (TEA), and reacted at room temperature for 10 hours. The reaction solution was extracted three times with dichloromethane and saturated sodium carbonate, dried and the organic phase was collected. And (4) spin-drying to obtain an amide product.
4) The amide product was charged to a reaction flask and Tetrahydrofuran (THF) was added. Slowly dropwise adding thionyl chloride (SOCl) 2 )91 μ L (1.25mmol) was reacted at room temperature for 1 hour, and after completion of the reaction, the reaction solution was diluted and quenched by addition of saturated sodium carbonate. Extracting the reaction solution, drying and collecting an organic phase. Spin-drying to obtain the chlorinated product.
5) The chlorinated product was charged into a reaction flask, 50mg (1.25mmol) of sodium hydroxide (NaOH) and methanol (MeOH) were added, reacted at 70 ℃ for 4 hours, extracted with saturated brine and dichloromethane 3 times, dried, and the organic phase was collected. Spin-drying, and separating the crude product by column chromatography to obtain a total of 301mg of product, with a yield of 60%.
The preparation method of the ligand L2 comprises the following steps:
1) 84mg (0.5mmol) of dibenzofuran and 2mL (2.5mmol) of n-butyllithium (n-BuLi) were charged into a reaction tube, and the mixture was reacted at-78 ℃ for 1 hour, and then the reaction tube was cooled to room temperature for 24 hours. After 24 hours, the mixture was placed at-78 ℃ and carbon dioxide (CO) was introduced 2 ) For 1 hour. Acidifying with hydrochloric acid (HCl) and pumping to obtain diacid product.
2) The diacid is put into a reaction tube, and thionyl chloride (SOCl) is added 2 ) mu.L (1.25mmol) was reacted at 70 ℃ for 3 hours to give the acid chloride product.
3) The acid chloride was slowly added dropwise to a reaction tube containing 488mg (1.5mmol) of amino alcohol ((1R,2S) -2-amino-1,2-bis (4- (tert-butyl) phenyl) ethane-1-ol) and 207. mu.L (1.5mmol) of Triethylamine (TEA), and reacted at room temperature for 10 hours. The reaction solution was extracted three times with dichloromethane and saturated sodium carbonate, dried and the organic phase was collected. And (4) spin-drying to obtain an amide product.
4) The amide product was charged to a reaction flask and Tetrahydrofuran (THF) was added. Slowly dropwise adding thionyl chloride (SOCl) 2 )91 μ L (1.25mmol) was reacted at room temperature for 1 hour, and after completion of the reaction, the reaction solution was diluted and quenched by addition of saturated sodium carbonate. Extracting the reaction solution, drying and collecting an organic phase. And (4) spin-drying to obtain a chlorinated product.
5) The chlorinated product was charged into a reaction flask, 50mg (1.25mmol) of sodium hydroxide (NaOH) and methanol (MeOH) were added, reacted at 70 ℃ for 4 hours, extracted with saturated brine and dichloromethane 3 times, dried, and the organic phase was collected. Spin-drying and separating the crude product by column chromatography to obtain 284mg total product, 65% yield.
Example 1
1.8mg (corresponding to 1.0 mol% of styrene) of ferrous trifluoromethanesulfonate and 6.0mg (corresponding to benzene) of ferrous trifluoromethanesulfonate were charged in the reaction tube1.2 mol% of ethylene) ligand L1 and 1mL of Dichloromethane (DCM) were stirred under inert gas for 30 minutes and the solvent was pumped off. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 52mg (0.5mmol) of styrene (1-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged at room temperature (25 ℃) and reacted for 48 hours. After the reaction, diluting with ethyl acetate, filtering with diatomite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography, and obtaining a product sample of 1-4, 221mg in total, 100% yield and enantioselectivity: 93: 7.
the detection data for product samples 1-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.07(d,J＝8.3Hz,4H),7.66(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.44-7.36(m,5H),5.03(dd,J＝9.4,4.0Hz,1H),4.08(dd,J＝15.5,9.7Hz,1H),3.73(dd,J＝15.6,4.0Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.2,136.5,134.1,129.1(two signals overlapped),129.0,128.6,127.2,65.6,53.2.
HRMS(ESI)calcd for[C 20 H 18 N 4 O 4 S 2 Na] + ([M+Na] + ):465.0662,found:465.0662.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 92/8, flow rate 0.5mL/min, detection wavelength 214nm), retention time 17.561min (major) and 19.169min (minor).
Example 2
1.8mg (equivalent to 1.0 mol% of m-chlorostyrene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% of m-chlorostyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes and the solvent was removed by pumping off. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 69mg (0.5mmol) of m-chlorostyrene (1-1) and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged to room temperature (2mmol)0 ℃ C. for 48 hours. After the reaction, diluting with ethyl acetate, filtering with diatomite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography, wherein the obtained product sample is recorded as 2-4, the total amount is 234mg, the yield is 98%, and the enantioselectivity is as follows: 94: 6.
the detection data for product samples 2-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.06(d,J＝7.9Hz,4H),7.66(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.35-7.30(m,3H),7.27-7.23(m,1H),4.98(dd,J＝9.4,4.2Hz,1H),4.02(dd,J＝15.6,9.5Hz,1H),3.69(dd,J＝15.6,4.3Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.1,138.5,135.0,134.1,130.4,129.2,129.0,128.5,127.3,125.3,65.0,53.2.
HRMS(ESI)calcd for[C 20 H 17 ClN 4 O 4 S 2 Na] + ([M+Na] + ):499.0272,found:499.0264.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 240nm) retention time 46.830min (major) and 34.421min (minor).
Example 3
1.8mg (equivalent to 1.0 mol% of m-methylstyrene), 4.8mg (equivalent to 1.2 mol% of m-methylstyrene), ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 59mg (0.5mmol) of m-methylstyrene (1-1) and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (30 ℃ C.) for 48 hours. After the reaction, the reaction mixture was diluted with ethyl acetate, filtered through celite, and concentrated by distillation under reduced pressure to remove the solvent, and the crude product was separated by column chromatography, and the obtained product was sampled as 3-4, and 171mg in total, the yield was 75%, and the enantioselectivity was: 90: 10.
the detection data for product samples 3-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.07(d,J＝8.0Hz,4H),7.66(t,J＝7.3Hz,2H),7.55(t,J＝7.7Hz,4H),7.30(t,J＝7.5Hz,1H),7.17(t,J＝8.4Hz,2H),7.15(s,1H),4.97(dd,J＝9.6,4.1Hz,1H),4.06(dd,J＝15.6,9.7Hz,1H),3.71(dd,J＝15.6,4.1Hz,1H),2.37(s,3H).
13 C NMR(100MHz,CDCl3)δ139.2,138.9,136.3,134.0,129.8,129.0(two signals overlapped),128.6,127.8,124.2,65.6,53.2,21.4.
HRMS(ESI)calcd for[C 21 H 20 N 4 O 4 S 2 Na] + ([M+Na] + ):479.0818,found:479.0820.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 97/3, flow rate 0.5mL/min, detection wavelength 214nm) retention time 22.767min (major) and 25.450min (minor).
Example 4
1.8mg (equivalent to 1.0 mol% of m-fluorostyrene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% of m-fluorostyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was purged. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 61mg (0.5mmol) of m-fluorostyrene (1-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged to react at room temperature (20 ℃ C.) for 48 hours. After the reaction is finished, diluting with ethyl acetate, filtering with diatomite, distilling and concentrating under reduced pressure to remove the solvent, separating the crude product by column chromatography, and recording the obtained product sample as 4-4, wherein the total amount is 205mg, the yield is 90%, and the enantioselectivity is as follows: 93: 7.
the detection data for product samples 4-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.09-8.07(m,4H),7.67(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.40-7.34(m,1H),7.15(d,J＝7.8Hz,1H),7.08-7.04(m,2H),5.02(dd,J＝9.5,4.1Hz,1H),4.04(dd,J＝15.6,9.6Hz,1H),3.70(dd,J＝15.6,4.1Hz,1H).
13 C NMR(100MHz,CDCl3)δ163.0(d,1JC-F＝246.6Hz),139.1,139.0(d,3JC-F＝6.9Hz),134.1,130.8(d,3JC-F＝8.2Hz),129.0,128.5,122.8(d,4JC-F＝3.0Hz),116.0(d,2JC-F＝20.9Hz),114.2(d,2JC-F＝22.2Hz),65.1(d,4JC-F＝1.6Hz),53.2.
19 F NMR(376MHz,CDCl3)δ-111.1.
HRMS(ESI)calcd for[C 20 H 17 FN 4 O 4 S 2 Na] + ([M+Na] + ):483.0567,found:483.0567.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 47.270min (major) and 35.267min (minor).
Example 5
1.8mg (equivalent to 1.0 mol% of m-methoxystyrene) of ferrous trifluoromethanesulfonate, 4.8mg (equivalent to 1.2 mol% of m-methoxystyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 61mg (0.5mmol) of m-methoxystyrene (5-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (30 ℃ C.) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample of 5-4, total 145mg, 62% yield, enantioselectivity: 91: 9.
the detection data for product samples 5-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.07(d,J＝7.8Hz,4H),7.66(t,J＝7.4Hz,2H),7.55(t,J＝7.7Hz,4H),7.32(t,J＝7.8Hz,1H),6.95(d,J＝7.6Hz,1H),6.92-6.89(m,2H),4.99(dd,J＝9.6,4.1Hz,1H),4.05(dd,J＝15.6,9.6Hz,1H),3.82(s,3H),3.72(dd,J＝15.6,4.1Hz,1H).
13 C NMR(100MHz,CDCl3)δ160.1,139.2,138.0,134.0,130.2,129.0,128.6,119.3,114.6,112.6,65.5,55.3,53.2.
HRMS(ESI)calcd for[C 21 H 20 N 4 O 5 S 2 Na] + ([M+Na] + ):495.0767,found:495.0768.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 62.008min (major) and 47.912min (minor).
Example 6
1.8mg (equivalent to 1.0 mol% of p-chlorostyrene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% of p-chlorostyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes and the solvent was pumped off. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 59mg (0.5mmol) of p-chlorostyrene (6-1) and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were placed in a flask and reacted at room temperature (15 ℃) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample of 6-4, total 203mg, 85% yield, enantioselectivity: 92: 8.
the detection data of the product 6-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.03(d,J＝8.1Hz,4H),7.67(t,J＝7.4Hz,2H),7.56(t,J＝8.0Hz,4H),7.36(d,J＝8.4Hz,2H),7.29(d,J＝8.4Hz,2H),5.01(dd,J＝9.1,4.7Hz,1H),3.99(dd,J＝15.6,9.1Hz,1H),3.72(dd,J＝15.6,4.7Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.0,135.0(two signals overlapped),134.1,129.4,129.0,128.6(two signals overlapped),64.9,53.0.
HRMS(ESI)calcd for[C 20 H 17 ClN 4 O 4 S 2 Na] + ([M+Na] + ):499.0272,found:499.0271.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 230nm) retention time 46.184min (major) and 41.438min (minor).
Example 7
1.8mg (equivalent to 1.0 mol% for p-trifluoromethylstyrene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% for p-trifluoromethylstyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes and the solvent was evacuated. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 86mg (0.5mmol) of p-trifluoromethylstyrene (7-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (25 ℃ C.) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, concentrating by distillation under reduced pressure to remove the solvent, separating the crude product by column chromatography to obtain a product sample of 7-4, 177mg in total, with a yield of 70%, enantioselectivity: 89: 11.
the detection data of product 7-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.04(d,J＝8.1Hz,4H),7.69-7.65(m,4H),7.56(t,J＝7.8Hz,4H),7.50(d,J＝8.0Hz,2H),5.11(dd,J＝9.1,4.5Hz,1H),4.02(dd,J＝15.6,9.2Hz,1H),3.75(dd,J＝15.6,4.3Hz,1H).
13 C NMR(100MHz,CDCl3)δ140.5,139.0,134.2,131.2(q,2JC-F＝32.5Hz),129.1,128.5,127.7,126.1(q,3JC-F＝3.7Hz),123.8(q,1JC-F＝270.7Hz),65.1,53.1.
19 F NMR(376MHz,CDCl3)δ-62.7.
HRMS(ESI)calcd for[C 21 H 17 F 3 N 4 O 4 S 2 Na] + ([M+Na] + ):533.0536,found:533.0534.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 98/2, flow rate 0.5mL/min, detection wavelength 230nm) retention time 34.898min (major) and 37.772min (minor).
Example 8
1.8mg (equivalent to 1.0 mol% of 3, 4-difluorostyrene) of ferrous trifluoromethanesulfonate, 4.8mg (equivalent to 1.2 mol% of 3, 4-difluorostyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, stirred under inert gas for 30 minutes and the solvent was evacuated. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 86mg (0.5mmol) of p-3, 4-difluorostyrene (8-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (20 ℃) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with diatomite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography, and obtaining a product sample of 8-4, 172mg in total, 72% yield, enantioselectivity: 92: 8.
the detection data for products 8-4 are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.56(d,J＝8.4Hz,2H),7.22(d,J＝8.4Hz,2H),4.83(dd,J＝8.1,4.4Hz,1H),2.62–2.49(m,1H),2.48–2.34(m,1H).
1 H NMR(400MHz,CDCl3)δ8.06(d,J＝8.0Hz,4H),7.68(t,J＝7.3Hz,2H),7.56(t,J＝7.7Hz,4H),7.20-7.14(m,2H),7.11-7.07(m,1H),4.99(dd,J＝9.1,4.5Hz,1H),3.99(dd,J＝15.6,9.2Hz,1H),3.69(dd,J＝15.6,4.5Hz,1H).
13 C NMR(100MHz,CDCl3)δ150.6(dd,1JC-F＝249.1Hz,2JC-F＝1.3Hz),150.5(dd,1JC-F＝248.9Hz,2JC-F＝1.9Hz),139.0,134.2,133.5(dd,3JC-F＝4.6Hz,4JC-F＝4.3Hz),129.1,128.5,123.4(dd,3JC-F＝6.4Hz,4JC-F＝3.7Hz),118.0(d,2JC-F＝17.5Hz),116.3(d,2JC-F＝17.Hz),64.6,53.2.
19 F NMR(376MHz,CDCl3)δ–135.4(d,3JF-F＝21.1Hz),-136.5(d,3JF-F＝21.1Hz).
HRMS(ESI)calcd for[C 20 H 16 F 2 N 4 O 4 S 2 Na] + ([M+Na] + ):501.0473,found:501.0473.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 230nm) retention time 41.152min (major) and 35.878min (minor).
Example 9
1.8mg (equivalent to 1.0 mol% of 3-chloro-4-fluorostyrene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% of 3-chloro-4-fluorostyrene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes, and the solvent was removed by pumping. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 86mg (0.5mmol) of 3-chloro-4-fluorostyrene (9-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (38 ℃ C.) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample of 9-4, total 205mg, 85% yield, enantioselectivity: 97: 3.
the test data for product 9-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.05(d,J＝7.7Hz,4H),7.67(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.37(dd,J＝6.8,2.0Hz,1H),7.26-7.22(m,1H),7.14(t,J＝8.5Hz,1H),4.99(dd,J＝9.1,4.7Hz,1H),3.99(dd,J＝15.6,9.1Hz,1H),3.71(dd,J＝15.6,4.7Hz,1H).
13 C NMR(100MHz,CDCl3)δ158.2(d,1JC-F＝249.5Hz),139.0,134.2,133.6(d,3JC-F＝3.9Hz),129.5,129.1,128.5,127.0(d,3JC-F＝7.4Hz),121.8(d,2JC-F＝17.9Hz),117.3(d,2JC-F＝21.3Hz),64.5,53.2.
19 F NMR(376MHz,CDCl3)δ-114.3.
HRMS(ESI)calcd for[C 20 H 16 ClFN 4 O 4 S 2 Na] + ([M+Na] + ):517.0178,found:517.0179.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 214nm) retention time 32.334min (major) and 28.365min (minor).
Example 10
1.8mg (equivalent to 1.0 mol% of 1-allyl-2-fluoro-4-vinylbenzene), 4.8mg (equivalent to 1.2 mol% of 1-allyl-2-fluoro-4-vinylbenzene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes, and the solvent was removed by pumping. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 86mg (0.5mmol) of 1-allyl-2-fluoro-4-vinylbenzene (10-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged at room temperature (25 ℃) and reacted for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, concentrating by distillation under reduced pressure to remove the solvent, separating the crude product by column chromatography to obtain a sample of 10-4, total 170mg, 68% yield, enantioselectivity: 89: 11.
the test data for product 10-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.08(d,J＝7.8Hz,4H),7.67(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.23(t,J＝7.7Hz,1H),7.08(d,J＝7.9Hz,1H),7.03(d,J＝10.4Hz,1H),6.00-5.90(m,1H),5.13(s,1H),5.10(d,J＝6.6Hz,1H),4.98(dd,J＝9.5,4.0Hz,1H),4.03(dd,J＝15.6,9.6Hz,1H),3.68(dd,J＝15.6,4.1Hz,1H),3.41(d,J＝6.6Hz,2H).
13 C NMR(100MHz,CDCl3)δ161.0(d,1JC-F＝246.1Hz),139.1,136.7(d,3JC-F＝7.0Hz),135.2,134.1,131.3(d,3JC-F＝5.2Hz),129.0,128.6,127.9(d,2JC-F＝16.0Hz),122.7(d,4JC-F＝3.5Hz),116.7,114.1(d,2JC-F＝23.2Hz),65.0(d,4JC-F＝1.6Hz),53.2,32.8(d,3JC-F＝2.7Hz).
19 F NMR(376MHz,CDCl3)δ-116.5.
HRMS(ESI)calcd for[C 23 H 21 FN 4 O 4 S 2 Na] + ([M+Na] + ):523.0880,found:523.0876.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 94/6, flow rate 0.5mL/min, detection wavelength 230nm) retention time 22.578min (major) and 19.405min (minor).
Example 11
1.8mg (equivalent to 1.0 mol% of 2-chloro-1-ethynyl-4-vinylbenzene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% of 2-chloro-1-ethynyl-4-vinylbenzene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes and the solvent was evacuated. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 81mg (0.5mmol) of 2-chloro-1-ethynyl-4-vinylbenzene (11-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged to room temperature (25 ℃) and reacted for 48 hours. After the reaction is finished, diluting with ethyl acetate, filtering with diatomite, distilling and concentrating under reduced pressure to remove the solvent, separating the crude product by column chromatography, and recording the obtained product sample as 11-4, wherein the total amount of the product sample is 200mg, the yield is 80%, and the enantioselectivity is as follows: 90: 10.
the test data for product 11-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.04(d,J＝7.7Hz,4H),7.68(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.53(d,J＝8.2Hz,1H),7.38(d,J＝1.1Hz,1H),7.23(dd,J＝8.0,1.3Hz,1H),5.01(dd,J＝9.0,4.7Hz,1H),3.98(dd,J＝15.6,9.0Hz,1H),3.72(dd,J＝15.6,4.8Hz,1H),3.43(s,1H).
13 C NMR(100MHz,CDCl3)δ138.9,138.7,137.0,134.5,134.2,129.1,128.5,128.0,125.3,122.8,83.5,79.5,64.8,53.0.
HRMS(ESI)calcd for[C 22 H 17 ClN 4 O 4 S 2 Na] + ([M+Na] + ):523.0271,found:523.0272.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 43.849min (major) and 30.092min (minor).
Example 12
1.8mg (equivalent to 1.0 mol% of 1, 3-dimethyl-5-vinylbenzene), 4.8mg (equivalent to 1.2 mol% of 1, 3-dimethyl-5-vinylbenzene), ligand L2 and 1mL of Dichloromethane (DCM) were charged into a reaction tube, stirred under inert gas for 30 minutes, and the solvent was evacuated. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL, 394mg (1.25mmol) of NFSI (1-3), 76mg (0.5mmol) of 1, 3-dimethyl-5-vinylbenzene (12-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (20 ℃ C.) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample of 12-4, total 165mg, 70% yield, enantioselectivity: 92: 8.
the test data for product 12-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.09(d,J＝7.8Hz,4H),7.66(t,J＝7.4Hz,2H),7.56(t,J＝7.7Hz,4H),7.01(s,1H),6.96(s,2H),4.94(dd,J＝9.7,4.0Hz,1H),4.08(dd,J＝15.5,9.8Hz,1H),3.71(dd,J＝15.6,4.1Hz,1H),2.33(s,6H).
13 C NMR(100MHz,CDCl3)δ139.3,138.8,136.2,134.0,130.7,128.9,128.5,124.9,65.6,53.2,21.3.
HRMS(ESI)calcd for[C 22 H 22 N 4 O 4 S 2 Na] + ([M+Na] + ):493.0975,found:493.0975.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 240nm) retention time 26.074min (major) and 21.231min (minor).
Example 13
1.8mg (equivalent to 1.0 mol% of 2-vinylbenzothiophene) of ferrous triflate, 4.8mg (equivalent to 1.2 mol% of 2-vinylbenzothiophene) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes and the solvent was evacuated. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL, 394mg (1.25mmol) of NFSI (1-3), 80mg (0.5mmol) of 2-vinylbenzothiophene (13-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at room temperature (30 ℃) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample of 13-4, a total of 245mg, 90% yield, enantioselectivity: 88: 12.
the detection data for product 13-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.07(d,J＝7.8Hz,4H),7.85-7.82(m,1H),7.75-7.73(m,1H),7.63(t,J＝7.4Hz,2H),7.50(t,J＝7.8Hz,4H),7.41-7.36(m,2H),7.30(s,1H),5.38(dd,J＝9.0,4.7Hz,1H),4.18(dd,J＝15.6,9.0Hz,1H),3.90(dd,J＝15.7,4.6Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.6,139.5,139.0,138.9,134.1,129.0,128.6,125.1,124.7,124.0,123.5,122.5,61.8,53.0.
HRMS(ESI)calcd for[C 22 H 18 N 4 O 4 S 3 Na] + ([M+Na] + ):521.0382,found:521.0382.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 214nm) retention time 32.490min (major) and 43.726min (minor).
Example 14
1.8mg (equivalent to 2.0 mol% of 3, 4-dichlorostyrene) of trifluoromethanesulfonic acid was added to the reaction tubeFerrous acid, 9.6mg (equivalent to 1.2 mol% for 3, 4-dichlorostyrene) of ligand L2 and 4mL of Dichloromethane (DCM) were stirred under inert gas for 30min, and the solvent was pumped off. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 8mL, 788.4mg (2.5mmol) of NFSI (1-3), 80mg (1mmol) of 3, 4-dichlorostyrene (14-1), and 346. mu.L (2.5mmol) of azidotrimethylsilane (1-2) were placed at room temperature (25 ℃ C.) and reacted for 48 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a product sample of 13-4, total 409mg, yield 80%, enantioselectivity: 93: 7.
the test data for product 14-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.04(d,J＝8.0Hz,4H),7.68(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.44(d,J＝8.2Hz,1H),7.41(d,J＝1.7Hz,1H),7.20(dd,J＝8.3,1.8Hz,1H),4.99(dd,J＝8.9,4.9Hz,1H),3.97(dd,J＝15.6,8.9Hz,1H),3.72(dd,J＝15.6,5.0Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.0,136.7,134.2,133.3(two signals overlapped),131.1,129.2,129.1,128.5,126.5,64.5,53.1.
HRMS(ESI)calcd for[C 20 H 16 C l2 N 4 O 4 S 2 Na] + ([M+Na] + ):532.9882,found:532.9879.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 42.526min (major) and 34.532min (minor).
Example 15
9mg (equivalent to 1.0 mol% of 1-bromo-2-methyl-4-vinylbenzene), 24mg (equivalent to 1.2 mol% of 1-bromo-2-methyl-4-vinylbenzene) of ligand L2 and 6mL of Dichloromethane (DCM) were charged into a reaction tube, stirred under inert gas for 30 minutes, and the solvent was removed by pumping. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 15mL, 1576.7mg (5mmol) of NFSI (1-3), 392mg (2mmol) of 1-bromo-2-methyl-4-vinylbenzene (14-1), and 553. mu.L (4mmol) of azidotrimethylsilane (1-2) were placed at room temperature (25 ℃) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with diatomite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography, and obtaining a product sample of 13-4, 818mg in total, with the yield of 80%, enantioselectivity: 93: 7.
the test data for product 15-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.04(d,J＝8.0Hz,4H),7.68(t,J＝7.4Hz,2H),7.56(t,J＝7.8Hz,4H),7.44(d,J＝8.2Hz,1H),7.41(d,J＝1.7Hz,1H),7.20(dd,J＝8.3,1.8Hz,1H),4.99(dd,J＝8.9,4.9Hz,1H),3.97(dd,J＝15.6,8.9Hz,1H),3.72(dd,J＝15.6,5.0Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.0,136.7,134.2,133.3(two signals overlapped),131.1,129.2,129.1,128.5,126.5,64.5,53.1.
HRMS(ESI)calcd for[C 20 H 16 C l2 N 4 O 4 S 2 Na] + ([M+Na] + ):532.9882,found:532.9879.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 42.526min (major) and 34.532min (minor).
Example 16
18mg (equivalent to 1.0 mol% of 1-fluoro-2-trifluoromethyl-4-vinylbenzene), 48mg (equivalent to 1.2 mol% of 1-fluoro-2-trifluoromethyl-4-vinylbenzene) of ligand L2 and 8mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 30 minutes, and the solvent was removed by pumping. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 30mL, 3.94g (12.5mmol) of NFSI (1-3), 1.9g (10mmol) of 1-fluoro-2-trifluoromethyl-4-vinylbenzene (16-1), and 1730. mu.L (12.5mmol) of azidotrimethylsilane, and then the mixture was reacted at room temperature (20 ℃ C.) for 48 hours. After the reaction, diluting with ethyl acetate, filtering with diatomite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography, and obtaining a product sample of 15-4, 3.81g in total, with the yield of 72%, enantioselectivity: 92: 8.
the test data for product 16-4 are as follows:
1 H NMR(400MHz,CDCl3)δ8.05(d,J＝8.1Hz,4H),7.67(t,J＝7.4Hz,2H),7.58-7.54(m,6H),7.21(t,J＝9.1Hz,1H),5.07(dd,J＝9.1,4.7Hz,1H),4.02(dd,J＝15.6,9.0Hz,1H),3.73(dd,J＝15.6,4.8Hz,1H).
13 C NMR(100MHz,CDCl3)δ159.8(dq,1JC-F＝257.0Hz,3JC-F＝2.3Hz),138.9,134.2,133.0(d,4JC-F＝3.9Hz),132.8(d,3JC-F＝8.8Hz),129.1,128.4,126.0(qd,3JC-F＝4.4Hz,3JC-F＝1.8Hz),122.1(q,1JC-F＝270.9Hz),119.0(qd,2JC-F＝33.0Hz,2JC-F＝12.7Hz),117.8(d,2JC-F＝20.9Hz),64.5,53.2.19F NMR(376MHz,CDCl3)δ-61.4(d,4JF-F＝12.7Hz),-113.3(q,4JF-F＝12.5Hz).
HRMS(ESI)calcd for[C 21 H 16 F 4 N 4 O 4 S 2 Na] + ([M+Na] + ):551.0441,found:551.0442.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 214nm) retention time 35.352min (major) and 28.555min (minor).
Example 17
7.2mg (equivalent to 1.0 mol% of 1- (chloromethyl) -4-vinylbenzene) of ferrous triflate, 24mg (equivalent to 1.5 mol% of 1- (chloromethyl) -4-vinylbenzene) of ligand L2 and 3mL of Dichloromethane (DCM) were added to the reaction tube, stirred under inert gas for 60 minutes, and the solvent was removed. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 9mL, 1576mg (5mmol) of NFSI (1-3), 305mg (2mmol) of 1- (chloromethyl) -4-vinylbenzene (17-1), 692. mu.L (5mmol) of azidotrimethylsilane (1-2), and then the reaction was carried out at room temperature (25 ℃ C.) for 48 hours. After the reaction is finished, useDiluting with ethyl acetate, filtering with celite, concentrating by distillation under reduced pressure to remove the solvent, separating the crude product by column chromatography to give a sample of 17-4 as 806mg, 82% yield: 92: 8.
the detection data for product sample 17-4 is as follows:
1 H NMR(400MHz,CDCl3)δ8.05(d,J＝8.0Hz,4H),7.66(t,J＝7.2Hz,2H),7.56(t,J＝7.8Hz,4H),7.43(d,J＝8.0Hz,2H),7.37(d,J＝8.1Hz,2H),5.03(dd,J＝9.4,4.3Hz,1H),4.60(s,2H),4.03(dd,J＝15.6,9.4Hz,1H),3.72(dd,J＝15.6,4.3Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.1,138.4,136.7,134.1,129.3,129.0,128.6,127.7,65.3,53.0,45.5.
HRMS(ESI)calcd for[C 21 H 19 ClN 4 O 4 S 2 Na] + ([M+Na] + ):513.0428,found:513.0429.[α]D25.8＝-43.18(c 0.4,CHCl3).
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 92/8, flow rate 0.5mL/min, detection wavelength 254nm) retention time 55.386min (major) and 45.011min (minor).
Example 18
3.6mg (equivalent to 1.0 mol% of 1- (difluoromethyl) -3-vinylbenzene) of ferrous triflate, 9.6mg (equivalent to 1.2 mol% of 1- (difluoromethyl) -3-vinylbenzene) of ligand L2 and 1.5mL of Dichloromethane (DCM) were charged into a reaction tube, stirred under inert gas for 30 minutes, and the solvent was evacuated. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 7mL, 788mg (2.5mmol) of NFSI (1-3), 156mg (1mmol) of 1- (difluoromethyl) -3-vinylbenzene (18-1), and 346. mu.L (2.5mmol) of azidotrimethylsilane (1-2) were placed at room temperature (25 ℃) and reacted for 48 hours. After the reaction, diluting with ethyl acetate, filtering with diatomite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography, and obtaining a product sample of 5-4, 424mg in total, 86% yield, enantioselectivity: 93: 7.
the detection data for product sample 18-4 is as follows:
1 H NMR(400MHz,CDCl3)δ8.07(d,J＝7.8Hz,4H),7.66(t,J＝7.5Hz,2H),7.57-7.49(m,8H),6.66(t,J＝56.2Hz,1H),5.09(dd,J＝9.5,4.2Hz,1H),4.08(dd,J＝15.6,9.5Hz,1H),3.75(dd,J＝15.6,4.3Hz,1H).
13 C NMR(100MHz,CDCl3)δ139.0,137.3,135.2(t,2JC-F＝22.4Hz),134.1,129.6,129.4,129.0,128.4,126.1(t,3JC-F＝5.9Hz),124.3(t,3JC-F＝6.1Hz),114.1(t,1JC-F＝237.8Hz),65.2,53.1.
19 F NMR(376MHz,CDCl3)δ-111.0(d,2JF-F＝14.4Hz).HRMS(ESI)calcd for[C 21 H 18 F 2 N 4 O 4 S 2 Na] + ([M+Na] + ):515.0630,found:515.0628.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 70.944min (major) and 49.570min (minor).
Example 19
1.8mg (equivalent to 1.0 mol% of 2-bromo-1-fluoro-4-vinylbenzene), 4.8mg (equivalent to 1.2 mol% of 2-bromo-1-fluoro-4-vinylbenzene), ligand L1, and 1mL of Dichloromethane (DCM) were charged into a reaction tube, stirred under an inert gas for 30 minutes, and the solvent was removed. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 5mL, 394mg (1.25mmol) of NFSI (1-3), 100mg (0.5mmol) of 2-bromo-1-fluoro-4-vinylbenzene (19-1), and 173. mu.L (1.25mmol) of azidotrimethylsilane (1-2) were charged and reacted at 50 ℃ for 36 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample of 2-4, total 165mg, 61% yield, enantioselectivity: 91: 9.
the detection data for product sample 19-4 is as follows:
1 H NMR(400MHz,CDCl3)δ8.05(d,J＝7.9Hz,4H),7.67(t,J＝7.4Hz,2H),7.58-7.51(m,5H),7.30-7.26(m,1H),7.11(t,J＝8.4Hz,1H),4.99(dd,J＝9.1,4.7Hz,1H),4.00(dd,J＝15.6,9.1Hz,1H),3.71(dd,J＝15.6,4.7Hz,1H).
13 C NMR(100MHz,CDCl3)δ159.2(d,1JC-F＝248.0Hz),139.0,134.1,134.0(d,3JC-F＝3.8Hz),132.3,129.0,128.5,127.8(d,3JC-F＝7.5Hz),117.1(d,2JC-F＝22.5Hz),109.8(d,,2JC-F＝21.2Hz),64.4,53.2.
19 F NMR(376MHz,CDCl3)δ–106.2.
HRMS(ESI)calcd for[C 20 H 16 BrFN 4 O 4 S 2 Na] + ([M+Na] + ):560.9673,found:560.9669.
HPLC (AD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 96/4, flow rate 0.5mL/min, detection wavelength 254nm) retention time 48.079min (major) and 40.399min (minor).
Example 20
3.6mg (corresponding to 5.0 mol% of the styrene-based starting material) of ferrous trifluoromethanesulfonate, 10.8mg (corresponding to 6 mol% of styrene) of ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL, 151mg (0.7mmol) of tert-butyl peroxy (2-ethylhexanoate) (1-4), 27mg (0.2mmol) of styrene compound (20-1), and 96. mu.L (0.7mmol) of azidotrimethylsilane (1-2), which was then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with celite, and concentrating by distillation under reduced pressure to remove the solvent, separating the crude product by column chromatography to obtain a sample of 20-4, 27.6mg total, 64% yield, enantioselectivity: 97: 3.
the detection data for product sample 20-4 are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.34–7.23(m,5H),4.36(s,1H),1.20(s,3H),1.17(s,3H).
13 C NMR(101MHz,Chloroform-d)δ134.5,127.7,127.6,127.4,72.7,62.6,22.6,21.7.
HRMS(DART)calcd for[C 10 H 13 N 6 ] + ([M-N 2 ] + ):189.1135,found:189.1133.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 1mL/min, detection wavelength 230nm), retention time 8.006min (major) and 9.375min (minor).
Example 21
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL of tert-butyl peroxy (2-ethylhexanoate) (1-4)151mg (0.7mmol), styrene compound (21-1)40mg (0.2mmol), and trimethylsilyl azide (1-2) 96. mu.L (0.7mmol), which were then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a product sample of 21-4, 31.2mg in total, 55% yield, enantioselectivity: 93: 7.
the detection data for product sample 21-4 are as follows:
1 H NMR(600MHz,Chloroform-d)δ7.68–7.48(m,4H),4.46(s,1H),1.28(s,3H),1.24(s,3H).
13 C NMR(151MHz,Chloroform-d)δ136.8,132.0,130.9(q,J＝32.1Hz),129.0,123.9(q,J＝271.8Hz),125.7(q,J＝3.1Hz),125.5(d,J＝3.0Hz),123.9(q,J＝271.8Hz),73.2,63.6,23.3,23.1.
HRMS(DART)calcd for[C 11 H 12 F 3 N 6 ] + ([M-N 2 ] + ):257.1009,found:257.1005.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 12.043min (major) and 13.471min (minor).
Example 22
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL of tert-butyl peroxy (2-ethylhexanoate) (1-4)151mg (0.7mmol), styrene (22-1)32mg (0.2mmol), and trimethylsilyl azide (1-2) 96. mu.L (0.7mmol), which were then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction is finished, diluting with ethyl acetate, filtering with diatomite, distilling and concentrating under reduced pressure to remove the solvent, separating the crude product by column chromatography, and recording the obtained product as 22-4 by 27.6mg in total, wherein the yield is 60%, and the enantioselectivity is as follows: 85: 15.
the assay data for product sample 22-4 is as follows:
1 H NMR(600MHz,Chloroform-d)δ7.29–7.24(m,1H),7.19–7.11(m,3H),4.39(s,1H),2.38(s,3H),1.26(s,3H),1.23(s,3H).
13 C NMR(151MHz,Chloroform-d)δ138.2,135.5,129.6,129.3,128.3,125.8,73.8,63.7,23.9,22.8,21.6.
HRMS(DART)calcd for[C 11 H 15 N 6 ] + ([M-N 2 ] + ):203.1291,found:203.1289.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 14.584min (major) and 15.399min (minor).
Example 23
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, and the mixture was stirred for 30 minutes under an inert gas condition, and the solvent was removed by pumping off. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL, 151mg (0.7mmol) of t-butyl peroxy (2-ethylhexanoate) (1-4), 42mg (0.2mmol) of styrene-based compound (23-1), and 96. mu.L (0.7mmol) of trimethylsilyl azide (1-2), which were then charged at room temperature (25 ℃ C.) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a total of 30.8mg of 23-4 as a sample, 54% yield, enantioselectivity: 89: 11.
the assay data for product sample 23-4 is as follows:
1 H NMR(600MHz,Chloroform-d)δ7.55–7.38(m,2H),7.20(dd,J＝8.3,2.1Hz,1H),4.34(s,1H),1.27(s,3H),1.23(s,3H).
13 C NMR(151MHz,Chloroform-d)δ136.0,133.1,132.8,130.6,130.6,130.5,130.5,128.0,128.0,72.5,63.5,23.4,23.2.
HRMS(DART)calcd for[C 10 H 11 Cl 2 N 6 ] + ([M-N 2 ] + ):257.0355,found:257.0352.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 15.865min (major) and 19.142min (minor).
Example 24
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under inert gas conditionsAdding magnetic stirrer, adding CHCl 3 2mL, 151mg (0.7mmol) of tert-butyl peroxy (2-ethylhexanoate) (1-4), 58mg (0.2mmol) of styrene compound (24-1), and 96. mu.L (0.7mmol) of azidotrimethylsilane (1-2), which was then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with celite, concentrating by distillation under reduced pressure to remove the solvent, separating the crude product by column chromatography to obtain a sample of 24-4, total 41.1mg, 55% yield, enantioselectivity: 88: 12.
the detection data for product sample 24-4 is as follows:
1 H NMR(600MHz,Chloroform-d)δ7.66(s,1H),7.43(s,2H),4.30(s,1H),1.28(s,3H),1.24(s,3H).
13 C NMR(151MHz,Chloroform-d)δ139.7,134.5,130.5,123.0,72.5,63.5,23.3.
HRMS(DART)calcd for[C 10 H 11 Br 2 N 6 ] + ([M-N 2 ] + ):344.9345,found:344.9339.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 15.413min (major) and 20.459min (minor).
Example 25
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL of tert-butyl peroxy (2-ethylhexanoate) (1-4)151mg (0.7mmol), styrene (25-1)28.8mg (0.2mmol), and trimethylsilyl azide (1-2) 96. mu.L (0.7mmol), which were then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction is finished, diluting with ethyl acetate, filtering with diatomite, carrying out reduced pressure distillation and concentration to remove the solvent, carrying out column chromatography separation on the crude product, and recording the obtained product sample25-4 in total, 34.2mg, 75% yield, enantioselectivity: 95: 5.
the assay data for product sample 25-4 is as follows:
1 H NMR(400MHz,Chloroform-d)δ7.46–7.32(m,5H),4.60(s,1H),2.46–2.33(m,1H),2.33–2.24(m,1H),2.24–2.14(m,1H),2.13–2.02(m,1H),2.01–1.87(m,1H),1.81–1.65(m,1H).
13 C NMR(101MHz,Chloroform-d)δ134.9,128.9,128.6,128.5,70.7,67.1,29.8,29.3,13.6.
HRMS(DART)calcd for[C 11 H 13 N 6 ] + ([M-N 2 ] + ):201.1135,found:201.1132.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 18.665min (major) and 22.614min (minor).
Example 26
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL of tert-butyl peroxy (2-ethylhexanoate) (1-4)151mg (0.7mmol), styrene (24-1)31.6mg (0.2mmol), and trimethylsilyl azide (1-2) 96. mu.L (0.7mmol), which were then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a sample 26-4, 26.6mg in total, 55% yield, enantioselectivity: 93: 7.
the detection data for product sample 26-4 is as follows:
1 H NMR(600MHz,Chloroform-d)δ7.42–7.35(m,5H),4.58(s,1H),1.99–1.89(m,1H),1.83–1.67(m,6H),1.55–1.46(m,1H).
13 C NMR(151MHz,Chloroform-d)δ136.1,128.9,128.6,128.4,75.3,72.6,34.7,34.5,23.5,23.4.
HRMS(DART)calcd for[C 12 H 15 N 6 ] + ([M-N 2 ] + ):215.1291,found:215.1289.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 16.954min (major) and 20.966min (minor).
Example 27
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ligand L2 and 1mL of Dichloromethane (DCM) were added to the reaction tube, and the mixture was stirred for 30 minutes under an inert gas condition, and the solvent was removed by pumping off. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL, 151mg (0.7mmol) of t-butyl peroxy (2-ethylhexanoate) (1-4), 36mg (0.2mmol) of styrene compound (27-1), and 96. mu.L (0.7mmol) of trimethylsilyl azide (1-2), which were then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction, the mixture was diluted with ethyl acetate, filtered through celite, and concentrated by distillation under reduced pressure to remove the solvent, and the crude product was separated by column chromatography to obtain a total of 38.5mg, dr:1.3:1, 73% yield, enantioselectivity: 92: 8.
the assay data for product sample 27-4 is as follows:
1 H NMR(400MHz,Chloroform-d)δ7.31(dd,J＝5.1,1.8Hz,2H),7.23–7.13(m,5H),6.99(dd,J＝6.6,2.9Hz,2H),4.59(d,J＝19.6Hz,2H).
13 C NMR(101MHz,Chloroform-d)δ135.84 135.8,129.0,128.7,128.7,128.6,128.0,127.7,70.7,69.7.
HRMS(DART)calcd for[C 14 H 13 N 6 ] + ([M-N 2 ] + ):237.1135,found:237.1132.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 18.401min (major) and 20.707min (minor).
Example 28
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL, 151mg (0.7mmol) of tert-butyl peroxy (2-ethylhexanoate) (1-4), 50mg (0.2mmol) of styrene compound (28-1), and 96. mu.L (0.7mmol) of azidotrimethylsilane (1-2), which was then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction, diluting with ethyl acetate, filtering with celite, distilling under reduced pressure and concentrating to remove the solvent, separating the crude product by column chromatography to obtain a total of 34.6mg of product, dr:1:1, yield 67%, enantioselectivity: 88: 12.
the detection data for product sample 28-4 is as follows:
1 H NMR(600MHz,Chloroform-d)δ7.36–7.34(m,1H),7.31(t,J＝7.7Hz,1H),7.27–7.24(m,3H),7.18(t,J＝7.8Hz,1H),7.14–7.07(m,2H),6.90(dt,J＝7.7,1.3Hz,1H),4.61(s,1H),4.57(s,1H).
13 C NMR(151MHz,Chloroform-d)δ137.6,137.5,134.8,134.7,130.1,130.0,129.4,129.2,128.1,127.8,126.2,126.0,70.0,69.0.
HRMS(DART)calcd for[C14H11N 6 Cl 2 ] + ([M-N 2 ] + ):305.0355,found:305.0351.
HPLC (IE,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 26.805min (major) and 29.579min (minor).
Example 29
3.6mg (corresponding to 5.0 mol% of the styrene-based raw material), 10.8mg (corresponding to 6 mol% of the styrene-based raw material) of ferrous trifluoromethanesulfonate, ligand L2 and 1mL of Dichloromethane (DCM) were charged into the reaction tube, and the mixture was stirred under an inert gas for 30 minutes, and the solvent was removed by suction. Under the condition of inert gas, adding a magnetic stirrer, and adding CHCl 3 2mL of tert-butyl peroxy (2-ethylhexanoate) (1-4)151mg (0.7mmol), styrene (29-1)23.4mg (0.2mmol), and trimethylsilyl azide (1-2) 96. mu.L (0.7mmol), which were then charged at room temperature (25 ℃) and reacted for 72 hours. After the reaction was completed, the mixture was diluted with ethyl acetate, filtered through celite, and concentrated by distillation under reduced pressure to remove the solvent, and the crude product was separated by column chromatography to obtain a sample of 29-4, which was 38mg total, dr:3:2, yield 61%, enantioselectivity: 85: 15 (main R, S), 92: 8 (minor R, R).
The assay data for product sample 29-4 is as follows:
(Main) 1 H NMR(600MHz,Chloroform-d)δ7.43–7.39(m,2H),7.38–7.36(m,1H)7.35–7.33(m,2H),4.54(d,J＝5.9Hz,1H),3.49(ddd,J＝9.4,5.9,1.5Hz,1H),1.93(s,3H),1.67(d,J＝12.3Hz,3H),1.62–1.57(m,3H),1.49–1.40(m,6H),1.35(dd,J＝15.0,1.5Hz,1H),1.19(dd,J＝14.9,9.4Hz,1H).
(Main) 13 C NMR(151MHz,Chloroform-d)δ136.1,129.0,128.9,127.8,70.3,61.4,43.7,42.4,36.9,28.8.
HRMS(DART)calcd for[C 19 H 25 N 6 ] + ([M-N 2 ] + ):309.2074,found:309.2070.
HPLC (OD-H,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 15.518min (major) and 13.641min (minor).
(second order) 1 H NMR(600MHz,Chloroform-d)δ7.42–7.36(m,3H),7.31–7.28(m,2H),4.42(s,1H),3.48(ddd,J＝9.3,7.5,1.6Hz,1H),1.91(s,3H),1.66(d,J＝12.3Hz,3H),1.58(d,J＝2.5Hz,2H),1.47–1.41(m,3H),1.38–1.33(m,3H),1.26–1.21(m,2H),1.09–1.04(m,1H).
13 C NMR(151MHz,Chloroform-d)δ136.6,129.1,129.0,127.8,71.2,61.8,44.8,42.4,36.9,32.0,28.5.
HRMS(DART)calcd for[C 19 H 25 N 6 ] + ([M-N 2 ] + ):309.2074,found:309.2070.
HPLC (IC,0.46 × 25cm,5 μm, n-hexane/isopropanol 100/0, flow rate 0.5mL/min, detection wavelength 220nm), retention time 13.641min (major) and 16.015min (minor).
Although the present application has been described with reference to a few embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the application as defined by the appended claims.
Claims (10)
1. An amine azide chiral compound, wherein the amine azide chiral compound is selected from any one of substances having a structural formula shown in formula I:
in formula I, R 1 Is selected from C 6 ～C 10 Aryl radicals I, C 6 ～C 10 Substituted aryl radicals I, C 8 ～C 12 Any one of heteroaryl I.
2. The amine azide chiral compound of claim 1, wherein C is 6 ～C 10 The substituted aryl I is selected from any one of groups with a structural formula shown in a formula II;
in formula II, R 2 Selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 3 selected from H, halogen, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Alkoxy radical, C 1 ～C 4 Haloalkyl, C 2 ～C 5 Alkenyl radical, C 2 ～C 5 Any one of alkynyl groups;
R 4 selected from H, C 1 ～C 4 Any of alkyl groups;
and, R 2 、R 3 、R 4 At most two of them are H;
preferably, in formula II, R 4 Is hydrogen;
or,
in formula II, R 3 Is hydrogen, R 2 Is selected from C 1 ～C 4 Any one of alkyl, R 4 Is selected from C 1 ～C 4 Any of alkyl groups;
preferably, said C 8 ～C 12 The heteroatoms in heteroaryl I include S;
preferably, said R is 1 Any one selected from the group having the following structural formula;
3. a process for the preparation of the amine azide chiral compound of any one of claims 1 to 2, wherein the process comprises: reacting a mixture containing N-fluoro-bis-benzenesulfonylimine, a compound II containing a carbon-carbon double bond and azidotrimethylsilane in the presence of a catalyst to obtain the amine azide chiral compound;
the catalyst comprises an iron source and a dibenzofuran oxazoline ligand;
the compound II containing the carbon-carbon double bond is selected from any one of substances with a structural formula shown in a formula III;
r in formula III 1 And R in formula I 1 The same is true.
4. The method of claim 3, wherein the iron source comprises Fe 3+ Source or Fe 2+ A source;
said Fe 3+ The source comprises any one of ferric acetate, ferric chloride and ferric fluoride;
said Fe 2+ The source comprises any one of ferrous trifluoromethanesulfonate, ferrous acetate, ferrous chloride and ferrous fluoride;
preferably, the dibenzofuran oxazoline ligand is selected from any one of substances with a structural formula shown in a formula V;
in formula V, R 5 And R 8 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 6 ～C 24 Aryl radical, C 6 ～C 24 Heteroaryl group, C 6 ～C 24 One of substituted aryl;
R 6 and R 7 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 6 ～C 24 Aryl radical, C 6 ～C 24 Heteroaryl group, C 6 ～C 24 One of substituted aryl;
preferably, the dibenzofuran oxazoline ligand is selected from any one of substances with structural formula shown in formula V-1;
in the formula V-1, R 51 、R 61 、R 71 、R 81 Are the same group;
R 51 、R 61 、R 71 、R 81 is selected from C 8 ～C 16 Any of substituted aryl groups;
preferably, said C 8 ～C 16 The substituted aryl is selected from any one of groups with a structural formula shown in a formula VI;
in formula VI, R 9 Is selected from C 4 ～C 7 Any of alkyl groups;
preferably, the molar ratio of the iron source to the dibenzofuran oxazoline ligand is 1:1 to 1.5;
preferably, the molar ratio of the N-fluoro-bis-benzenesulfonylimine to the azidotrimethylsilane to the compound II containing the carbon-carbon double bond is 1-10: 1-10: 1;
preferably, the molar ratio of the iron source to the compound II containing the carbon-carbon double bond is 0.5-10: 100;
preferably, the reaction conditions are: the reaction temperature is not more than 50 ℃, and the reaction time is not less than 6 minutes;
preferably, the reaction conditions are: the reaction temperature is 20-50 ℃, and the reaction time is 48-72 h;
preferably, the mixture also contains an organic solvent;
the organic solvent comprises at least one of chloroform, dichloromethane, carbon tetrachloride and diethyl ether;
preferably, the ratio of the volume of the organic solvent to the mole number of the compound II containing the carbon-carbon double bond is 1.0-2.0 mL/mmol;
preferably, the preparation method comprises:
s100, mixing an iron source and a dibenzofuran oxazoline ligand with an organic solvent a, stirring under an inert condition, and pumping away the organic solvent a to obtain a material a;
s200, adding an organic solvent b, N-fluoro-bis-benzenesulfonylimine, a compound II containing a carbon-carbon double bond and azidotrimethylsilane into the material a under an inert condition, and reacting to obtain the amine azide chiral compound.
5. A chiral organic matter of diazide, wherein the chiral organic matter of diazide is selected from any one of substances with structural formula shown in formula i (a) or formula i (b);
in formula i (a), R 'and R' are independently selected from H, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Substituted alkyl, C 6 ～C 10 Aryl radical, C 6 ～C 10 Any of substituted aryl groups;
said C is 1 ～C 4 The substituent in the substituted alkyl is adamantyl;
R 1 the same as in formula I;
in formula i (b), n is 0 or 1; r 1 The same as in formula I.
6. The method for preparing chiral organic compounds of diazide according to claim 5, comprising:
reacting a mixture containing tert-butyl peroxy (2-ethylhexanoate), azidotrimethylsilane and a substance a containing carbon-carbon double bonds in the presence of a catalyst to obtain the chiral organic matter of bis-azido;
the catalyst comprises an iron source and a dibenzofuran oxazoline ligand;
the substance a containing the carbon-carbon double bond is selected from any one of substances shown in formula i-1 or formula i-2;
wherein R is 1 Same as in formula I;
r ', R' are the same as in formula i (a);
n is the same as formula i (b);
preferably, the substance a containing a carbon-carbon double bond is selected from any one of the following substances;
preferably, the iron source comprises Fe 3+ Source or Fe 2+ A source;
said Fe 3+ The source comprises ferric triflate;
said Fe 2+ The source comprises ferrous triflate;
preferably, the dibenzofuran oxazoline ligand is selected from any one of substances with a structural formula shown in a formula V;
in formula V, R 5 And R 8 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 1 ～C 24 Aryl radical, C 1 ～C 24 Heteroaryl, C 1 ～C 24 One of substituted aryl;
R 6 and R 7 Each independently selected from hydrogen and C 1 ～C 12 Alkyl radical, C 1 ～C 24 Aryl radical, C 1 ～C 24 Heteroaryl group, C 1 ～C 24 One of substituted aryl groups.
7. The method according to claim 6, wherein the molar ratio of tert-butyl peroxy (2-ethylhexanoate), trimethylsilyl azide and the compound a having a carbon-carbon double bond is 0.5 to 1.0:0.1 to 0.3.
8. The method according to claim 6, wherein the molar ratio of the iron source to the compound a having a carbon-carbon double bond is 1 to 10: 100.
9. The method according to claim 6, wherein the reaction conditions are as follows: the reaction temperature is not more than 50 ℃, and the reaction time is not less than 6 minutes.
10. The method according to claim 6, wherein the reaction conditions are as follows: the reaction temperature is 20-50 ℃, and the reaction time is 48-72 h.
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